We have delineated certain of the virologic and immunologic events associated with primary HIV infection. In the simian immunodeficiency virus (SIV) model numerous individual infected cells localized in peripheral lymph nodes of monkeys as early as day 7 post-inoculation. Trapping of virions in the follicular dendritic cell (FDC) network was initially detected at week 2 post-inoculation and progressively increased over time, whereas the number of SIV-infected cells decreased. Trapping of virions in the FDC network was temporally associated with a rise in the levels of complement-binding antibodies. Similar kinetics of HIV distribution in lymph nodes were observed in individuals with primary HIV infection. High levels of human immunodeficiency virus (HIV) DNA and RNA synthesis occurred in peripheral blood mononuclear cells and dramatic downregulation of the levels of HIV RNA synthesis coincided with the emergence of HIV-specific immune responses. We have demonstrated major expansions in T cells manifesting a restricted set of Vbeta families during the primary immune response to HIV. Cells expressing the expanded Vbetas were predominantly CD8+ T lymphocytes, were involved in the expression of cytokines, and mediated specific cytotoxic activity. Nucleotide sequences of recombinant clones of the expanded Vbeta families demonstrated the oligoclonal (i.e., antigen-specific) nature of these expansions. Expansion of these Vbeta families was driven by HIV antigens. Disappearance/deletion of HIV-specific T cell clones occurred in the absence of virus mutations. These expanded HIV-specific clonotypes were predominantly expressed in blood compared to lymph node. Similarly, during primary infection the pool of HIV-specific cytotoxic T cells segregated in blood as opposed to lymph node. These observations shed considerable light on the potential mechanisms of viral escape from the immune response during primary HIV infection. Three patterns of Vbeta expansions were observed. These different patterns appear to be predictive of different clinical outcomes.